Psilocin and 25I-NBOMe produced distinct neurotransmitter patterns in the rat claustrum, with psilocin appearing more balanced and 25I-NBOMe more excitation-biased.
Evidence
In vivo microdialysis and testing in adult male Wistar Han rats measured extracellular DA, NA, 5-HT, GLU, GABA, and ACh after local claustrum administration of psilocin or 25I-NBOMe.
Caveat
The findings come from local drug administration in male rats and wet dog shakes are only a proxy for psychedelic-like activity, not human therapeutic or toxicological outcomes.
Simplified
BACKGROUND: The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, emotional regulation, salience, and attention. Despite its hypothesized involvement in the effects of serotonergic psychedelics, the neurochemical impact of these substances on claustral neurotransmission remains unexplored. This study aimed to investigate how psilocin — a tryptamine and the active metabolite of psilocybin — and 4-Iodo-2, 5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) — a phenethylamine and new psychoactive substance (NPS) — modulate extracellular neurotransmitter levels in the rat claustrum, as well as to examine their effects on behavior, a well-established proxy for hallucinogenic activity.
METHODS: Adult male Wistar Han rats were used for in vivo brain microdialysis experiments. Microdialysis probes were stereotaxically implanted into the claustrum. Rats received local administration of either psilocin (100 or 500 µM) or 25I-NBOMe (500 µM) through the microdialysis probe. Dialysate samples were collected and analyzed using high-performance liquid chromatography (HPLC) with electrochemical detection to quantify extracellular levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT), glutamate (GLU), gamma-aminobutyric acid (GABA), and acetylcholine (ACh). A behavioral test defined as wet dog shakes (WDS) was conducted after drugs administration, to infer psychedelic-like activity.
RESULTS: In vivo microdialysis performed in freely moving rats revealed that both substances markedly altered extracellular levels of DA, NA, 5-HT, GLU, GABA, and ACh. Psilocin, at both administered doses, was the only compound to significantly elevate NA and produced the most pronounced enhancement of cholinergic signaling across all neurotransmitter systems examined. By contrast, 25I-NBOMe induced a more substantial shift toward excitatory dominance, accompanied by the greatest increase in 5-HT release. Overall, psilocin generated a comparatively balanced excitatory–inhibitory neurochemical profile, reflecting its combined engagement of 5-HT2A and 5-HT1A receptors, whereas 25I-NBOMe produced an excitation-biased pattern consistent with its selective, high-affinity 5-HT2A agonism.
CONCLUSIONS: These findings highlight the claustrum as a neurochemical convergence point for psychedelic action and demonstrate that psilocin engages this circuitry in a regulated, receptor-balanced manner, whereas 25I-NBOMe drives a markedly more excitatory and less compensated profile, underscoring their fundamentally distinct therapeutic and toxicological potentials.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43440-025-00817-3.
Key numbers
20 min
Increase in Level
Psilocin (100 µM) induces a significant increase in levels.
1.48
/ Ratio Increase
25I-NBOMe significantly elevates the / ratio.
Full Text
We can’t show the full text here under this license.
